Review Article

Immune-based combination therapy to convert immunologically cold tumors into hot tumors: an update and new insights

Jiao-jiao Ni1,2,3,4, Zi-zhen Zhang2,3,4, Ming-jie Ge5, Jing-yu Chen2,3,4, Wei Zhuo1,3,4
1 Department of Cell Biology and Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
2 Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China
3 Institution of Gastroenterology, Zhejiang University, Hangzhou 310016, China
4 Cancer Center, Zhejiang University, Hangzhou 310058, China
5 Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Hangzhou 310006, China
Correspondence to: Wei Zhuo:,
DOI: 10.1038/s41401-022-00953-z
Received: 28 April 2022
Accepted: 3 July 2022
Advance online: 4 August 2022


As a breakthrough strategy for cancer treatment, immunotherapy mainly consists of immune checkpoint inhibitors (ICIs) and other immunomodulatory drugs that provide a durable protective antitumor response by stimulating the immune system to fight cancer. However, due to the low response rate and unique toxicity profiles of immunotherapy, the strategies of combining immunotherapy with other therapies have attracted enormous attention. These combinations are designed to exert potent antitumor effects by regulating different processes in the cancer-immunity cycle. To date, immune-based combination therapy has achieved encouraging results in numerous clinical trials and has received Food and Drug Administration (FDA) approval for certain cancers with more studies underway. This review summarizes the emerging strategies of immune-based combination therapy, including combinations with another immunotherapeutic strategy, radiotherapy, chemotherapy, anti-angiogenic therapy, targeted therapy, bacterial therapy, and stroma-targeted therapy. Here, we highlight the rationale of immune-based combination therapy, the biomarkers and the clinical progress for these immune-based combination therapies.
Keywords: immunotherapy; immune checkpoint inhibitors; combination therapy; biomarkers; neoplasms

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